We reviewed the American College of Physicians (ACP) guidelines on the treatment of low bone density or osteoporosis to prevent fractures (1). Strengths of these guidelines include their rigorous methods; their use of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach (2); and that they are based on an extensive systematic review. However, we are worried that adherence to these guidelines may not yield the balance of benefits and costs that the authors judged as favorable when they made strong treatment recommendations, and we have a few questions to clarify this issue.